Program Director/Principal Investigator (Last, First, Middle): Longini, Ira, M., et al. PROJECT SUMMARY (Seeinstructions): The overall objective of this research is to develop, validate, and implement mathematical and statistical models for the transmission and within-host dynamics of naturally occurring infectious diseases and bioterrorism agents. These models will be used to assess the effectiveness and efficacy of various interventions to aid the distribution and allocation of resources in response to infectious disease outbreaks. The specific aims are as follows: 1. To develop epidemic mathematical models for the transmission of naturally occurring infectious diseases and bioterrorism agents: a. To develop or further develop mathematical models for important infectious disease threats including influenza, cholera, dengue fever, TB and new emerging infectious disease threats. b. To use the epidemic mathematical and statistical models to evaluate the effectivenessof interventions involving surveillance and containment, vaccination, antimicrobials, social distancing, and other control strategies for the infectious diseases in specific aim 1 .a. c. To use and develop statistical methods to estimate the important parameters and variables from data available for the infectious diseases. d. To develop frameworks to make the developed mathematical and statistical models available to public health organizations and researchers e. To develop a comprehensive framework using graph theory for the estimation of social contact networks for acute infectious diseases. 2. To develop models at the within-host level which allow us to link the dynamics of infection of individual hosts with the transmission of the pathogen in the host population: a. To construct models to examine the within-host dynamics of pathogens. b. To extend the models developed in specific aim 2.a.to include antiviral treatment and prophylaxis as well as vaccination. c. To explicitly link the models of within-host dynamics of infection with its spread between hosts. RELEVANCE (Seeinstructions): The introduction of naturally occurring infectious diseases or bioterrorism agents into the population continues to pose a considerable public health threat to the nation and the world. This research will prove analytical and mathematical tools to help with the rapid assessent of how these infectious agents are spreading and how to contain them in real time. This work also will provide methods for control should containment fail. PROJECT/